Fcε receptor I (hereinafter also referred to as “FcεRI”), one of receptors (FcεR) for Fc portion (Fcε) of immunoglobulin E (IgE), has high affinity to IgE. FcεRI is a glycoprotein molecule expressed principally on the cellular membrane of mast cells and basophiles and plays an important role in type I allergic reaction for activation of these cells. Upon crosslinkage of antigen-specific IgE with corresponding multivalent antigens, i.e. allergens, FcεRI aggregates and signal transduction mechanism begins to act to thereby activate mast cells. As a result, a cellular degranulation occurs to thereby release chemical mediators such as histamine and serotonin, inducing novel synthesis and release of leukotrienes, prostaglandins and the like to provoke type I allergic reaction.
Human FcεRI consists of three distinct subunits, i.e. an IgE binding factor α chain, a signal amplifying factor β chain, and a signal transmitting factor Υ chain, forming either a tetramer consisting of each one α and β chains and two Υ chains, or a trimer consisting of one α chain and two Υ chains.
On the surface of the cellular membrane of mast cells and basophiles, tetrameric FcεRI is principally expressed and plays an important role in type I allergic reaction for activation of these cells as described above.
On the cellular membrane of skin Langerhans cells, monocytes, eosinophiles, dendritic cells, and platelets, expression of trimeric FcεRI is principally observed though at a lower level than that of tetrameric FcεRI and is suggested to contribute to antigen display and production of chemical mediators.
It is believed that the a chain alone in FcεRI directly interacts with IgE and its binding region to IgE spans overall the extracellular region of the α chain (Nature, vol. 406 (2000), p. 259).
As for function of FcεRI within the living body, analysis with the α chain-knockout mouse suggested that FcεRI may contribute to protection mechanism from infection with certain parasite. However, a phenotype is not found under normal conditions in the knockout mouse and hence an FcεRI gene is not a gene indispensable to survival in mice.
As described above, interaction between IgE and FcεRI is important for onset of disease in case of allergic diseases. It is also known that FcεRI-expressing cells increase in patient blood. Besides, it is known that expression of FcεRI is enhanced in eosinophiles, monocytes and basophiles in peripheral blood of patients suffering from atopic asthma, allergic rhinitis and atopic dermatitis, suggesting its involvement in onset of diseases.
It is reported that autoantibody against FcεRI α chain occurs in serum from some patients with chronic hives. Thus, activation of FcεRI-expressing cells due to crosslinkage of FcεRI with anti-FcεRI autoantibody has been postulated as a mechanism for onset of disease.